A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)

A Phase One-B (1B) Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)

The investigators will conduct a single-center, prospective, randomized, placebo-controlled, double-blind pilot study of anti-herpesvirus therapy in patients with idiopathic pulmonary fibrosis (IPF). Patients with mild, moderate or severe IPF with serologic evidence of current or past Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) infection. Randomization will be to pirfenidone plus placebo or pirfenidone plus valganciclovir. Thirty subjects will be enrolled and randomized to treatment with pirfenidone plus valganciclovir (20 subjects) or pirfenidone plus placebo (10 subjects) for 12 weeks. The primary outcome will be safety and tolerability will be determined by type, frequency and duration of adverse events (AEs) and serious adverse events (SAEs) after 12 weeks of study drug treatment. All study subjects will be offered bronchoscopy with bronchoalveolar lavage (BAL) at study initiation and upon completion of treatment (12 weeks). Subjects will then be followed up at routine clinic visits at 6, 9 and 12 months for data collection.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Valganciclovir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age >21 and <80 years
2. ability to provided informed consent
3. diagnosis of probable or definite IPF according to American Thoracic Society (ATS) criteria
4. tolerance of full-dose (2403 mg/day) pirfenidone
5. Positive serology for EBV or CMV

Exclusion Criteria:

1. FVC < 40% predicted
2. Diffusing capacity for carbon monoxide (DLCO) < 35% predicted (Crapo)
3. Forced expiratory volume (FEV)1/FVC <0.7
4. Significant centrilobular emphysema (>40% by HRCT)
5. Active tobacco use (cigarette or cigar smoking)
6. Resting oxygen saturation (SpO2) on room air <89%
7. Listed for lung transplantation defined as being assigned a lung allocation score
8. environmental exposure (occupational, environmental, drug, etc.) felt by the principal investigator (PI) to be the etiology of the interstitial disease
9. diagnosis of collagen-vascular conditions (according to the published American College of Rheumatology criteria)
10. history of unstable or deteriorating cardiac disease
11. acute coronary syndrome, coronary artery bypass, or angioplasty within 3 months of screening
12. uncontrolled arrhythmia
13. uncontrolled hypertension
14. known HIV or hepatitis C
15. known cirrhosis or chronic active hepatitis
16. active substance or alcohol abuse
17. pregnancy or lactation
18. Women of childbearing potential who are not using a medically approved means of contraception. Subjects will be considered of childbearing potential if they are not surgically sterile or have not been postmenopausal for at least 2 years [any subject who is postmenopausal for < 2 years will be required to have a follicle-stimulating hormone (FSH) level to assess her potential to become pregnant

19. clinically relevant lab abnormalities (obtained within 30 days before enrollment), including:

    1. creatinine > 2 x upper limit of normal (ULN)
    2. hematology outside of specified limits: white blood cells (WBCs) < 3,500/mm3; hematocrit < 25% or > 59%; platelets < 100,000/mm3;
    3. total bilirubin > 2 x ULN
    4. Aspartate (AST) or alanine aminotransferases (ALT)/ serum glutamic-oxaloacetic; transaminase (SGOT), or serum glutamic pyruvic transaminase (SGPT) > 2.0 x ULN
    5. alkaline phosphatase > 3 x ULN
    6. albumin < 3.0 mg/dL at screening
20. known hypersensitivity to study medication
21. any condition that, in the judgment of the PI, might cause participation in this study to be detrimental to the subject or that the PI deems makes the subject a poor candidate
22. any therapy with immunosuppressants such as prednisone, azathioprine, or mycophenolate currently or anticipated to be needed during the study period (subjects on these drugs prior to the study will require a 30-day washout period before randomization)
23. participation in another IPF clinical treatment trial during the study period (if completing another IPF clinical treatment trial, then a 30-day washout period is required before randomization)
24. requirement for chronic suppressive therapy with valacyclovir for recurrent herpes virus infection
25. History of myelodysplasia, aplastic anemia, refractory anemia, or multiple myeloma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valganciclovir; Valganciclovir 450 mg, 2 pills by mouth one time per day x 12 weeks	Drug: Valganciclovir; Subjects with IPF currently tolerating pirfenidone treatment who have evidence of prior EBV or CMV infection will be randomized to valganciclovir or placebo for 12 weeks.; Other Names: Valcyte
Placebo Comparator: Placebo; Placebo, 2 pills by mouth one time per day x 12 weeks	Drug: Placebo; Subjects with IPF currently tolerating pirfenidone treatment who have evidence of prior EBV or CMV infection will be randomized to valganciclovir or placebo for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Discontinue Study Drug Due to Adverse Events	Proportion of study subjects who discontinue study drug due to adverse events	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events - Number	Number of subjects with each reported adverse event	12 weeks
Serious Adverse Events	Number of subjects with each serious adverse event	12 weeks
Total # Adverse Events	Total number of adverse events	Randomization to 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Forced Vital Capacity (FVC)	Change in FVC percent predicted compared to baseline	Baseline vs. 12 weeks, 1 year

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Jonathan A Kropski, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Blackwell TS, Hewlett JC, Mason WR, Martin S, Del Greco J, Ding G, Wu P, Lancaster LH, Loyd JE, Dudenhofer RB, Salisbury ML, Kropski JA. A Phase I Randomized, Controlled, Clinical Trial of Valganciclovir in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2021 Aug;18(8):1291-1297. doi: 10.1513/AnnalsATS.202102-108OC.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: IPF; Herpesvirus; Valganciclovir
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: 160693

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No